Clinical Pharmacology of Hi Receptor Antagonists Clinical Uses Allergic Reactions ‘The H, antihistaminic agents are often the first drugs used to prevent or treat the symptoms of allergic reactions, In allergic rhinitis and urticaria, in which histamine is the primary mediator, the 11; antagonists are the drugs of choice and are often quite effective. However, in bronchial asthma, which involves several mediators, the Hf; antagonists are largely ineffective. Angioedema may be precipitated by histamine release but appears to be maintained by peptide kinins that are not affected by antihistaminic agents. For atopic dermatitis, antihistaminie drugs such as diphenhydramine are used mostly for their sedative side effects and for some control of the itching. ‘The H; antihistamines used for treating allergic conditions such as hay fever are usually selected with the goal of minimizing sedative effects; in the USA, the drugs in widest use are the alkylamines and the second-generation nonsedating agents. However, the sedative effect and the therapeutic efficacy of different agents vary widely among individuals. In addition, the clinical effectiveness of one group may diminish with continued use, and switching to another group may restore drug effectiveness for as yet unexplained reasons. ‘The second-generation H; antagonists are used mainly for the treatment of allergic rhinitis and chronic urticaria, Several double-blind comparisons with older agents (such as chlorpheniramine) indicated about equal therapeutic efficacy. However, sedation and interference with safe operation of machinery, which occur in about 50% of subjects taking first-generation antihistamines, occurred in only about 7% of subjects taking second generation agents. The newer drugs are much more expensive. Motion Sickness and Vestibular Disturbances. Scopolamine and certain first-generation H antagonists are the most effective agents available for the prevention of motion sickness. The antihistaminic drugs with the greatest effectiveness in this application are diphenhydramine and promethazine. Dimenhydrinate, which is promoted for the treatment of motion sickness, is a salt of diphenhydramine. The piperazines (cyelizine and meclizine) also have significant activity in preventing motion sickness and are less sedative in most patients. Dosage is the same as that recommended for allergic disorders (Table 16-2). Both scopolamine and the Hy antagonists are more effective in preventing motion sickness when combined with ephedrine or amphetamine Ithas been claimed that the antinistaminic agents effective in prophylaxis of motion sickness are also useful in Meniere's syndrome, but efficacy in the latter application is not well established. Nausea and Vomiting of Pregnancy Several Hy antagonist drugs have been studied for possible use in treating "moming sickness." The piperazine derivatives were withdrawn from such use when it was demonstrated that they have teratogenic effects in rodents. Doxylamine, an ethanolamine H; antagonist, was promoted for this application as a component of Bendectin, a prescription medication that also contained pyridoxine. Possible teratogenic effects of doxylamine were widely publicized in the lay press after 1978 as a